Chlamydia trachomatis sexually transmitted infections cause considerable morbidity and socioeconomic burden worldwide, despite significant advances in our understanding of the pathogenesis and epidemiology of this bacterial pathogen. Chlamydial urogenital infections are readily cured with antibiotics, but control measures based upon antimicrobial chemotherapy alone are hampered by the frequency of asymptomatic infections and delayed diagnosis. Definitive control of C. trachomatis sexually transmitted diseases is possible through the development of a safe and effective vaccine. A heightened understanding of protective immunity to chlamydial genital infection has emerged this past decade from studies using a mouse model of Chlamydia muridarum infection. The insights gained from studies using the mouse model of infection are of considerable interest because they offer promise for the development of an efficacious vaccine. Using the mouse model of chlamydial genital infection, we have shown that anti-chlamydia antibody markedly protects animals during genital tract reinfection. In our proposed studies we will further define and characterize the protective antibody-mediated response through 4 specific aims. Aim 1 focuses on optimizing the response by determining the optimum timing and dose of antibody therapy (convalescent serum); Aim 2 uses an immunomics approach to identify chlamydial antigens recognized by the protective convalescent serum; in Aim 3 we will test recombinant preparations of protective antigens identified in Aim 2 for their ability to induce protective antibody responses; and lastly, we have shown that the protective effect of antibody is dependent on a yet to be identified cell population and in Aim 4 we will begin to characterize the cellular component that interacts with protective antibody to resolve secondary chlamydial reinfection. Sustained control of chlamydial urogenital infections will be achieved only by the development of an efficacious vaccine. The studies outlined in this proposal will provide important insight toward achieving that goal.